Research Inefficiency in Degenerative Cervical Myelopathy: Findings of a Systematic Review on Research Activity Over the Past 20 Years.

STUDY DESIGN: Scoping review. OBJECTIVE: To describe activity, themes and trends in degenerative cervical myelopathy (DCM) research over the past 20 years with a view to considering DCM research inefficiency. METHODS: A systematic review of MEDLINE and Embase for "Cervical" AND "Myelopathy" was conducted following PRISMA guidelines. Full-text papers in English, exclusively studying DCM, published between January 1, 1995 and December 31, 2015 were considered eligible. Country of origin, number of papers published, number of patients studied, research theme, and year of publication were assessed. Comparison was made between developed and developing countries. RESULTS: A total of 1485 papers and 4 117 051 patients were included. Japan published more papers (450) than any other country while the United States studied the greatest number of patients (3 674 737). Over 99.4% of papers and 78.6% of patients were from developed countries. The number of papers (r = 0.96, P < .001) and patients (r = 0.83 P < .001) studied each year increased significantly overall and for both developed (r = 0.93, P < .001; r = 0.81, P < .001) and developing countries (r = 0.90, P < .001; r = 0.87, P < .001). Surgery was the most prevalent theme (58.3% papers; 55.7% patients) for developed and developing countries. Research from developing countries showed greater thematic variability. CONCLUSIONS: DCM research activity is increasing internationally, with surgery remaining the focus. Research output has predominantly been from developed countries; however, the rate of growth for developed and developing countries is comparable

Scottish theme towns: have new identities enhanced development?

Three small towns in southwest Scotland have recently been branded as distinct theme towns, based on books, artists and food. This is an attempt to make them more attractive to visitors and thereby improve their economy. The objective of this research is to establish whether the new identities possessed by the towns have enhanced their development. It is argued, using data reviewing the past decade, that they have all developed, albeit at different rates, in terms of the economy and culture. Moreover, it is maintained that social capital has been enhanced and is a factor whose importance has been under-appreciated by planners and observers of this type of process. The relevance of the new identity to the pre-branding identity is also seen as a factor in successful development and ideas of authenticity and heritage are brought to bear on the relationship

Development of a core measurement set for research in degenerative cervical myelopathy: a study protocol (AO Spine RECODE-DCM CMS)

INTRODUCTION Progress in degenerative cervical myelopathy (DCM) is hindered by inconsistent measurement and reporting. This impedes data aggregation and outcome comparison across studies. This limitation can be reversed by developing a core measurement set (CMS) for DCM research. Previously, the AO Spine Research Objectives and Common Data Elements for DCM (AO Spine RECODE-DCM) defined 'what' should be measured in DCM: the next step of this initiative is to determine 'how' to measure these features. This protocol outlines the steps necessary for the development of a CMS for DCM research and audit. METHODS AND ANALYSIS The CMS will be developed in accordance with the guidance developed by the Core Outcome Measures in Effectiveness Trials and the Consensus-based Standards for the selection of health Measurement Instruments. The process involves five phases. In phase 1, the steering committee agreed on the constructs to be measured by sourcing consensus definitions from patients, professionals and the literature. In phases 2 and 3, systematic reviews were conducted to identify tools for each construct and aggregate their evidence. Constructs with and without tools were identified, and scoping reviews were conducted for constructs without tools. Evidence on measurement properties, as well as on timing of assessments, are currently being aggregated. These will be presented in phase 4: a consensus meeting where a multi-disciplinary panel of experts will select the instruments that will form the CMS. Following selection, guidance on the implementation of the CMS will be developed and disseminated (phase 5). A preliminary CMS review scheduled at 4 years from release. ETHICS AND DISSEMINATION Ethical approval was obtained from the University of Cambridge (HBREC2019.14). Dissemination strategies will include peer-reviewed scientific publications; conference presentations; podcasts; the identification of AO Spine RECODE-DCM ambassadors; and engagement with relevant journals, funders and the DCM community

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies

Degenerative cervical myelopathy (DCM) is estimated to be the most common cause of adult spinal cord impairment. Evidence that is suggestive of a genetic basis to DCM has been increasing over the last decade. A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and HuGENet databases from their origin up to 14th December 2019 to evaluate the role of single genes in DCM in its onset, clinical phenotype, and response to surgical intervention. The initial search yielded 914 articles, with 39 articles being identified as eligible after screening. We distinguish between those contributing to spinal column deterioration and those contributing to spinal cord deterioration in assessing the evidence of genetic contributions to DCM. Evidence regarding a total of 28 candidate genes was identified. Of these, 22 were found to have an effect on the radiological onset of spinal column disease, while 12 genes had an effect on clinical onset of spinal cord disease. Polymorphisms of eight genes were found to have an effect on the radiological severity of DCM, while three genes had an effect on clinical severity. Polymorphisms of six genes were found to have an effect on clinical response to surgery in spinal cord disease. There are clear genetic effects on the development of spinal pathology, the central nervous system (CNS) response to bony pathology, the severity of both bony and cord pathology, and the subsequent response to surgical intervention. Work to disentangle the mechanisms by which the genes that are reviewed here exert their effects, as well as improved quality of evidence across diverse populations is required for further investigating the genetic contribution to DCM

The Role of Nutrition in Degenerative Cervical Myelopathy: A Systematic Review.

INTRODUCTION: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord impairment worldwide, encompassing chronic compression of the spinal cord, neurological disability and diminished quality of life. Evidence on the contribution of environmental factors is sparse; in particular, the role of nutrition in DCM is unknown. The objective of this review was to assess the effect of nutrition on DCM susceptibility, severity and surgical outcome. METHODS: A systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English papers, focussing on cervical myelopathy and nutrition, published before January 2020 were considered eligible. Quality assessments were performed using the GRADE assessment tool. Patient demographics, nutritional factor and DCM outcomes measures were recorded. Relationships between nutritional factors, interventions and disease prognosis were assessed. RESULTS: In total, 5835 papers were identified of which 44 were included in the final analysis. DCM patients with pathological weight pre-operatively were more likely to see poorer improvements post-surgically. These patients experienced poorer physical and mental health improvements from surgery compared to normal weight patients and were more likely to suffer from post-operative complications such as infection, DVT, PE and hospital readmissions. Two trials reporting benefits of nutritional supplements were identified, with 1 suggesting Cerebrolysin to be significant in functional improvement. An unbalanced diet, history of alcohol abuse and malnourishment were associated with poorer post-operative outcome. CONCLUSION: Although the overall strength of recommendation is low, current evidence suggests nutrition may have a significant role in optimising surgical outcome in DCM patients. Although it may have a role in onset and severity of DCM, this is a preliminary suggestion. Further work needs to be done on how nutrition is defined and measured, however, the beneficial results from studies with nutritional interventions suggest nutrition could be a treatment target in DCM.Funding: Dr Benjamin M. Davies is supported by an NIHR Clinical Doctoral Research Fellowship. This report is independent research arising from a Clinician Scientist Award, CS-2015-15-023, supported by the National Institute for Health Research

Methylation panel is a diagnostic biomarker for Barrett’s oesophagus in endoscopic biopsies and non-endoscopic cytology specimens

Objective Barrett’s Oesophagus is a premalignant condition that occurs in the context of gastro-oesophageal reflux. However, most Barrett’s cases are undiagnosed because of reliance on endoscopy. We have developed a non-endoscopic tool; the Cytosponge™ which when combined with TFF3 immunohistochemistry can diagnose Barrett’s. We investigated whether a quantitative methylation test that is not reliant on histopathological analysis could be used to diagnose Barrett’s oesophagus. Design Differentially methylated genes between Barrett’s and normal squamous oesophageal biopsies were identified from whole methylome data and confirmed using MethyLight PCR in biopsy samples of squamous oesophagus, gastric cardia and Barrett’s oesophagus. Selected genes were then tested on Cytosponge™ BEST2 trial samples comprising a pilot cohort (n=20 cases, n=10 controls) and a validation cohort (n=149 cases, n=129 controls). Results Eighteen genes were differentially methylated in patients with Barrett’s compared to squamous controls. Hypermethylation of TFPI2, TWIST1, ZNF345 and ZNF569 was confirmed in Barrett’s biopsies compared with biopsies from squamous oesophagus and gastric cardia (p<0.05). When tested in Cytosponge™ samples these four genes were hypermethylated in patients with Barrett’s oesophagus compared to patients with reflux symptoms (p<0.001). The optimum biomarker to diagnose Barrett’s was TFPI2 with a sensitivity and specificity of 82.2% and 95.7 % respectively. Conclusion TFPI2, ZNF345 and ZNF569 CpG methylation has promise as a diagnostic biomarker panel for Barrett’s when used in combination with a simple and cost effective non-endoscopic cell collection device.The BEST2 study was funded by Cancer Research UK (C14478/ A12088). RCF receives core funding from the Medical Research Council. The study received infrastructure support from the Cambridge Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the Experimental Cancer Medicine Centre

RE-CODE DCM (search Objectives and ommon ata lements for egenerative ervical yelopathy): A Consensus Process to Improve Research Efficiency in DCM, Through Establishment of a Standardized Dataset for Clinical Research and the Definition of the Research Priorities

Study Design ixed-method consensus process. Objectives egenerative cervical myelopathy (DCM) is a common and disabling condition that arises when mechanical stress damages the spinal cord as a result of degenerative changes in the surrounding spinal structures. RECODE-DCM (search Objectives and ommon ata lements for egenerative ervical yelopathy) aims to improve efficient use of health care resources within the field of DCM by using a multi-stakeholder partnership to define the DCM research priorities, to develop a minimum dataset for DCM clinical studies, and confirm a definition of DCM. Methods his requires a multi-stakeholder partnership and multiple parallel consensus development processes. It will be conducted via 4 phases, adhering to the guidance set out by the COMET (Core Outcomes in Effectiveness Trials) and JLA (James Lind Alliance) initiatives. Phase 1 will consist of preliminary work to inform online Delphi processes (Phase 2) and a consensus meeting (Phase 3). Following the findings of the consensus meeting, a synthesis of relevant measurement instruments will be compiled and assessed as per the COSMIN (Consensus-based Standards for the Selection of Health Measurement Instruments) criteria, to allow recommendations to be made on how to measure agreed data points. Phase 4 will monitor and promote the use of eventual recommendations. Conclusions ECODE-DCM sets out to establish for the first time an index term, minimum dataset, and research priorities together. Our aim is to reduce waste of health care resources in the future by using patient priorities to inform the scope of future DCM research activities. The consistent use of a standard dataset in DCM clinical studies, audit, and clinical surveillance will facilitate pooled analysis of future data and, ultimately, a deeper understanding of DCM

Development of a validated search filter for Ovid Embase for degenerative cervical myelopathy.

Funder: Royal College of Surgeons of England; Id: http://dx.doi.org/10.13039/501100000297BACKGROUND: Degenerative cervical myelopathy (DCM) is a recently proposed umbrella term for symptomatic cervical spinal cord compression secondary to degeneration of the spine. Currently literature searching for DCM is challenged by the inconsistent uptake of the term 'DCM' with many overlapping keywords and numerous synonyms. OBJECTIVES: Here, we adapt our previous Ovid medline search filter for the Ovid embase database, to support comprehensive literature searching. Both embase and medline are recommended as a minimum for systematic reviews. METHODS: References contained within embase identified in our prior study formed a 'development gold standard' reference database (N = 220). The search filter was adapted for embase and checked against the reference database. The filter was then validated against the 'validation gold standard'. RESULTS: A direct translation was not possible, as medline indexing for DCM and the keywords search field were not available in embase. We also used the 'focus' function to improve precision. The resulting search filter has 100% sensitivity in testing. DISCUSSION AND CONCLUSION: We have developed a validated search filter capable of retrieving DCM references in embase with high sensitivity. In the absence of consistent terminology and indexing, this will support more efficient and robust evidence synthesis in the field